ZNF750 inhibits the proliferation and invasion of melanoma cells through modulating the Wnt/β-catenin signaling pathway
ZNF750 inhibits the proliferation and invasion of melanoma cells through modulating the Wnt/β-catenin signaling pathway
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DOI：
10.5603/fhc.a2020.0026
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发表时间：
2020-01-01
影响因子：
1.5
通讯作者：
Liu, Jing
中科院分区：
文献类型：
--
作者：
Du, Yong;Lv, Guozhong;Liu, Jing
导言。锌指蛋白750(ZNF750)在肿瘤中的异常表达已有报道。本研究旨在探讨ZNF750在黑色素瘤发生发展中的作用。采用实时定量聚合酶链式反应和免疫组织化学方法检测ZNF750在皮肤恶性黑色素瘤中的表达水平。明确ZNF750表达与临床病理特征的关系。采用细胞计数试剂盒(CCK-8)、集落形成实验和侵袭实验观察ZNF750对黑色素瘤细胞增殖、集落形成、迁移和侵袭的影响。用Western印迹法检测ZNF750对上皮-间充质转化相关蛋白的调节作用。ZNF750在人黑色素瘤组织和细胞中的表达下调，并与黑色素瘤患者的临床病理特征包括肿瘤大小、淋巴结转移和Clark分级有关。此外，ZNF750过表达降低了黑色素瘤细胞的增殖、侵袭和抑制EMT，而ZNF750过表达则表现出相反的作用。重要的是，机制分析表明，ZNF750上调抑制了β-连环蛋白及其下游靶蛋白(细胞周期蛋白D1、c-Myc、Bcl-2、MMP2和MMP9)的表达，表明它可以阻断Wnt/β-连环蛋白通路的激活。一致地，ZNF750基因的敲除导致了相反的结果。总之，ZNF750通过调节Wnt/β-catenin途径，对黑色素瘤的发生和发展起到了肿瘤抑制作用。这项研究证实了ZNF750参与了黑色素瘤的进展，并可能为黑色素瘤的治疗提供一个有前途的治疗靶点。
Introduction. The abnormal expression of Zinc Finger Protein 750 (ZNF750) has been reported in neoplastic diseases. This study investigated the functional role of ZNF750 in the progression of melanoma.Material and methods. Quantitative real-time PCR and immunohistochemistry (IHC) were performed to detect the expression levels of ZNF750 in patients diagnosed with primary cutaneous malignant melanoma. The correlation between clinical-pathological features and ZNF750 expression were clarified. Cell Counting Kit-8 (CCK-8), colony formation and transwell assays were used to explore the effects of ZNF750 on the proliferation, colony formation, migration and invasion of melanoma cells. Western blot assay was used to evaluate the effects of ZNF750 on regulating epithelial-mesenchymal transition (EMT) related proteins.Results. ZNF750 expression was down-regulated in human melanoma tissues and cells, and correlated with the clinical-pathological features including tumor size, lymph node metastasis, and Clark classification in patients with melanoma. In addition, overexpression of ZNF750 decreased the proliferation, invasion and suppressed EMT of melanoma cells, whereas ZNF750 depletion showed the opposite effects. Importantly, mechanistic analyses implied that upregulation of ZNF750 inhibited the expression of beta-catenin and the downstream targets (cyclin D1, c-Myc, Bcl-2, MMP2 and MMP9), indicating it could block the activation of Wnt/beta-catenin pathway. Consistently, knockdown of ZNF750 led to the opposite results.Conclusions. Together, ZNF750 serves as a tumor suppressor for the development and progression of melanoma through regulating the Wnt/beta-catenin pathway. This study confirms the involvement of ZNF750 in melanoma progression and may provide a promising therapeutic target for the treatment of melanoma.